Incidence of herpes genitalis in Northern Ireland in 1973-83 and herpes simplex types 1 and 2 isolated in 1982-4.

During 1973 - 83 there was a pronounced rise in the number of new cases of herpes genitalis in Northern Ireland. This study of 127 patients with herpes genitalis shows that 30% had herpes simplex virus type 1 (HSV 1) and 70% had herpes simplex virus type 2 (HSV 2) infections. Of 41 sexual contacts who attended, only seven had herpes genitalis (caused in each case by HSV 2); another patient had a history of genital lesions, and one other of oral lesions, but HSV was not isolated from either patient. None of the other sexual contacts had a history of oral or genital infection. Of 31 women with herpes genitalis who consented to undergoing cervical cytology, five had atypical changes (all had primary herpes genitalis). Of these, four were infected with HSV 1 and one with HSV 2.     

Detection of varicella zoster virus in genital specimens using a multiplex polymerase chain reaction

OBJECTIVE: To compare the relative proportions of varicella zoster virus (VZV) and herpes simplex viruses in specimens obtained from the genital lesions of adults presenting with presumed genital herpes infection. METHODS: Swabs of genital lesions from 6210 patients attending general practices, infectious diseases clinics within hospitals, or sexual health centres for treatment of their genital lesions were tested using polymerase chain reaction (PCR) technology. The multiplexed PCR was capable of detecting herpes simplex virus types 1 and 2 (HSV-1, HSV-2), VZV, and cytomegalovirus in a single sample. RESULTS: A total of 2225 patients had viruses detected by PCR. HSV-1 was detected in 36%, HSV-2 in 61%, and VZV in 2.9% of PCR positive samples. Of the 65 patients with VZV genital infection, many were thought to have HSV infection before laboratory testing. CONCLUSIONS: The finding of VZV in nearly 3% of virus positive genital specimens demonstrates that this virus needs to be considered as a differential diagnosis for genital herpetic lesions. Advice provided to patients with VZV genital infection regarding the source of infection, likelihood of recurrence, and potential for transmission of the virus will be different from that given to patients with HSV infection.     

First episodes of genital herpes in a Swedish STD population: a study of epidemiology and transmission by the use of herpes simplex virus (HSV) typing and specific serology

OBJECTIVES: To determine the proportion of herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2) in first episodes of genital herpes. To evaluate the use of HSV specific serology for classifying first episodes of genital herpes and for defining HSV serostatus in the patients' sexual partners. METHODS: 108 consecutive patients with first episodes of genital herpes seen at three STD clinics in Sweden from 1995 to 1999 were included in the study. HSV culture and typing were performed and serum was tested for antibodies against a type common HSV antigen and a type specific HSV-2 antigen, glycoprotein G2 (gG2). A structured interview including questions about sexual behaviour and sexual partners was taken. "Steady" partners were offered a blood test for HSV serology and counselling. RESULTS: Of 108 patients, 11 had a negative HSV culture. Of the 97 who were HSV culture positive, 44% (43/97) were typed as HSV-1 and 56% (54/97) as HSV-2. For 86 of these 97 patients, HSV serology from the initial visit was available. Of 52 primary infections, thus initially seronegative, 64% were HSV-1 infections and of 19 female primary infections 16 (84%) were HSV-1. In 17% the first episode of genital herpes corresponded to the first clinical recurrence of an infection acquired earlier in life. There was a significant correlation between having orogenital sex and being infected with HSV-1 and also a history of labial herpes in the partner. Only 20% of partners of patients with an HSV-2 infection had a history of genital herpes. CONCLUSIONS: Almost half of first episodes of genital herpes are caused by HSV-1. In young women with a primary genital infection, HSV-1 is much more frequent than HSV-2. Besides HSV typing, we found specific HSV serology of value for classifying first episodes and for diagnosing a subclinical HSV-2 infection in partners. Anamnestic data supported the suggestion that the orogenital route of transmission was common in genital HSV-1 infections.     

Epidemiology of genital herpes - recent advances

Genital herpes is a common, distressing infection which, due to increasing incidence world-wide, has become a prominent public health issue over recent years, even throughout the decade of human immunodeficiency virus (HIV). Since the late 1970's, the prevalence of herpes simplex virus type 2 (HSV-2) infection has increased by approximately 30 percent in the US. The number of sufferers world-wide is currently estimated at approximately 86 million people. New serological methods based on the detection of type-specific antibodies to herpes simplex virus (HSV) glycoproteins have clarified issues concerning the true incidence of genital herpes, the modifying effect of prior HSV-1 infections, the changing proportions of HSV-1 genital herpes, and the importance of asymptomatic shedding. Patients' ignorance of their diagnosis along with the occurrence of atypical symptomatology and asymptomatic viral shedding of HSV all contribute to the transmission of genital herpes. Genital ulcer disease, of which genital herpes is the most common cause in developed countries, is an important risk factor in the acquisition and transmission of human immunodeficiency virus (HIV) infection and has contributed to the spread of this disorder. Risk factors for genital herpes HSV-2 are strongly related to lifetime number of sexual partners, number of years of sexual activity, male homosexuality, black race, female gender and a history of previous sexually transmitted diseases (STD). Understanding the epidemiology of genital herpes is of great importance in limiting the spread of this STD. In this review, we summarise current knowledge related to the epidemiology of genital herpes.     

Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students

A retrospective review of genital herpes simplex virus (HSV) isolates collected in a university student health service over a 9-year period showed that an increasing proportion of isolates were HSV-1 rather than HSV-2. HSV-1 accounted for 78% of all genital isolates in this population by 2001, compared with 31% of isolates in 1993. BACKGROUND: Herpes simplex virus (HSV) type 1 is usually thought to cause less than 30% of genital herpes infections in the United States, but the proportion of infections resulting from HSV-1 is increasing in some populations. GOAL: The goal was to review the relative proportion of HSV-1 and HSV-2 as the cause of newly diagnosed genital herpes infections in a population of U.S. college students and to assess trends in the change of this proportion over time. STUDY DESIGN: Genital HSV isolates collected at a university student health service from 1993 to 2001 (n = 499) were reviewed retrospectively. Analyses included comparisons of isolates by HSV type, age group, and sex. RESULTS: The proportion of newly diagnosed genital herpes infections resulting from HSV-1 increased from 31% in 1993 to 78% in 2001 (P <0.001, linear trend P <0.001). HSV-1 was more common in females than males, but increases were noted for both sexes. HSV-1 was more common in persons aged 16 to 21 than in persons aged 22 or older. CONCLUSIONS: HSV-1 has become the most common cause of newly diagnosed genital herpes infections in this population of college students and reflects a reversal of the usual HSV-1/HSV-2 ratio.     

Famciclovir reduces viral mucosal shedding in HSV-seropositive persons

OBJECTIVE: Many cases of herpes simplex virus (HSV) infection occur through asymptomatic shedding from persons without evidence of clinical disease. This study explores whether famciclovir reduces HSV shedding in HSV-2 seropositive persons with or without a history of symptomatic genital herpes. STUDY DESIGN: One hundred twenty-seven HSV-2 seropositive participants were randomly assigned to 42 days of famciclovir, followed by 14 days of washout and 42 days of placebo, or vice versa. All subjects swabbed the genital/perianal area; those with HSV-1 infection also swabbed the oral area daily for HSV DNA PCR. RESULTS: Famciclovir reduced genital and oral HSV shedding from 11.4% of days during the placebo period to 4.7% of days during famciclovir therapy. The reduction was greater in participants with a history of genital herpes (74%) than in those without such a history (30%). In multivariate analyses, famciclovir protected against total (clinical and subclinical) genital shedding among persons with a clinical history of genital herpes (RR, 0.23; 95% CI, 0.15-0.35; P < 0.001). Among HSV-2 seropositive participants without a history of genital herpes, 60% had HSV detected in the genital area at least once during the study. Famciclovir therapy did not result in a statistically significant reduction in total HSV shedding in participants without a history of genital herpes. CONCLUSION: Famciclovir therapy decreases genital HSV shedding in HSV-seropositive persons, especially those with a history of genital herpes. Overall, antiviral drugs may have varying effects on symptomatic and asymptomatic viral shedding, depending on the clinical history of the disease.     

Sequential genital infections by herpes simplex viruses types 1 and 2: restriction nuclease analyses of viruses from recurrent infections

Virus isolated from a woman presenting with the first symptomatic episode of genital herpes was identified as herpes simplex virus type 1 (HSV-1) by restriction nuclease fingerprinting. Testing for IgM antibody to HSV indicated that the patient had recently contracted a new HSV infection. Virus microneutralization and the micro-solid phase radioimmunometric test for IgG, however, showed that the patient had had prior infection with herpes simplex virus type 2 (HSV-2); thus the HSV-1 infection was acquired despite the presence of antibody to HSV-2. Genital herpes recurred about four, seven, and nine months after the HSV-1 infection. Isolates from the latter three episodes all were of an identical strain of HSV-2 and were not recombinants or a mixture of the viruses. The data show that two distinctly different herpes simplex viruses can initiate genital infections in one individual and suggest that HSV-2 is more likely to recur than HSV-1.     

Seroprevalence of herpes simplex virus type 1 and type 2 in Turkey

BACKGROUND: Herpes simplex virus (HSV) infections are among the most common infectious diseases in humans. The prevalence of herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) varies widely across the world. HSV-2 infection is the primary cause of genital herpes. It is highly prevalent in human populations in many parts of the world, and is the most common cause of genital ulcer disease worldwide. In spite of the large prevalence and growing incidence of herpes simplex infection (HSV-1 and HSV-2), relatively few data have been published regarding the seroprevalence of herpes simplex infection, while no data exist regarding the Turkish population. METHODS: We aimed to investigate the prevalence of HSV-1 and HSV-2 in selected populations in Turkey. A cross-sectional study was conducted involving 2082 serum samples of 725 adults, 300 pregnant women, 200 blood donors, 483 sex workers and 110 patients with genital warts and 264 hotel staff in Istanbul, Turkey. All serum samples were assessed for HSV1 and HSV-2 IgG antibodies using an HSV-type specific, enzyme-linked immunosorbent assay (ELISA). RESULTS: The prevalence of HSV-2 and HSV-1 antibodies was 4.8 and 85.3% in sexually active adults; 5.5 and 96% in blood donors; 5 and 98% in pregnant women, 17.3 and 93.6% in patients with genital warts; 8.3 and 97.3% in hotel staff; and 60% and 99% in sex workers. CONCLUSION: These results confirm a higher prevalence of HSV infection than estimated, especially in high risk groups in Turkey. The high prevalence of HSV infection underlines the need for education among these populations.     

Recurrent genital herpes in a population attending a clinic for sexually transmitted diseases.

Patients with recurrent genital herpes attending a sexually transmitted disease clinic were studied and transmission of the infection was elucidated by evaluating serostatus in their partners. Of 84 patients attending for recurrent genital herpes, 94% had a herpes simplex virus type 2 (HSV-2) infection and only 6% (5 patients) a type 1 infection. The mean age of the patients was 36 years and the duration of their infection was up to 37 years (median 4 years). In most patients the number of recurrences had not decreased between the first year and the last year. About half had experienced a more severe first episode infection. Of the patients, 64% were not aware of asymptomatic shedding and the risk of sexual transmission without clinical symptoms. Of 67 steady partners of patients with genital HSV-2, 15% had a history of genital herpes. By HSV serology, HSV-2 antibodies (indicating subclinical genital herpes) were demonstrated in more than half of the partners. The duration of the relationship or condom use did not seem to influence the frequency of transmission to the partner, which may indicate an individual susceptibility for acquiring a genital HSV-2 infection. Eleven per cent of the patients were on suppressive antiviral therapy, while 39% had no experience of antiviral therapy. Type-specific HSV serology was found to be of value in counselling partners of patients with genital herpes.     

Chancroidal ulcers that are not chancroid. Cause and epidemiology

Hemophilus ducreyi was isolated from the ulcer of one of 33 patients in whom chancroid had been diagnosed clinically. Herpes simplex virus was isolated from 16 of these patients. A presumptive diagnosis of chancroid was made in one of three sexual partners of the only index patient with culture-proved chancroid. No chancroidal lesions were found in any of 39 sexual partners of the other 32 index patients. Genital cultures for herpes simplex virus were positive from four of 14 sexual partners of index patients with genital herpes simplex infection. The differential diagnosis of chancroidal genital ulcers is facilitated by herpes simplex virus cultures and a new selective H ducreyi culture medium.     

Asymptomatic shedding and subsequent transmission of genital herpes simplex virus.

We report the transmission of genital herpes simplex virus (HSV) infection from an asymptomatic woman shedding virus from the cervix to two male sexual partners and further transmission from these two men while their infection was in the prodromal phase. The value of the restriction enzyme analysis of viral deoxyribonucleic acid (DNA) is presented. Guidelines regarding the management of patients who are found to be asymptomatic shedders of HSV are discussed.     

Incidence and prevalence of herpes simplex virus infections in adolescent women

OBJECTIVES: We conducted this study to examine the incidence, prevalence, and risk factors for herpes simplex virus (HSV) 1 and HSV 2 infection in a cohort of young women who were closely followed for acquisition of sexually transmitted infections. STUDY DESIGN: Women between the ages of 14 and 18 years had blood and genital specimens obtained quarterly to test for incident sexually transmitted infections. Subjects also had 2 12-week periods each year when they kept a detailed behavioral diary and performed weekly vaginal swabs. Serum specimens were tested for HSV 1 and HSV 2 antibody, and genital specimens were tested for HSV DNA by PCR. RESULTS: A total of 100 subjects enrolled and had at least 2 sera that could be analyzed for seroconversion. The mean age of the subjects was 15.8 years at entry. The HSV 1 and HSV 2 seroprevalence at entry was 59.6% and 13.5%, respectively. During the study, 4 subjects acquired HSV 1 antibody and 7 acquired HSV 2 antibody, but there were no cases of symptomatic HSV infection identified. The annualized incidence among susceptible individuals was 8.9% for HSV 1 and 7.4% for HSV 2. Three of the 7 HSV 2 sero-converters had HSV 2 DNA detected in vaginal swabs. Age, duration of sexual activity, and the presence of other sexually transmitted infections were predictors of HSV 2 antibody positivity. CONCLUSIONS: Acquisition of HSV 1 and HSV 2 is relatively common in adolescent women, although symptomatic infection is uncommon. HSV 2 is shed in the genital tract despite the lack of symptoms.     

Update on antiviral therapy for herpes simplex virus infection

ABSTRACT: The prevalence of infection with herpes simplex virus (HSV) continues to increase largely due to the inability of current antiviral agents to eradicate latent infection. This article reviews strategies to slow the transmission of HSV infection, most importantly through the development of vaccines, as well as established and emerging choices for treatment of primary and recurrent genital herpes, herpes labialis, infections in immunocompromised hosts, and acyclovir-resistant infections. The role of chronic suppressive therapy in the management of genital herpes as well as its potential impact on transmission rates will also be discussed.
Herpes simplex virus (HSV) is a widespread pathogen in the United States, with more than 100 million U.S. citizens having serologic evidence of HSV-1 infection and 40–60 million, nearly one-fifth of the adolescent and adult population, infected with HSV-2 (1,2) . The prevalence of HSV-2, the major cause of genital herpes, has increased 30% since the late 1970s (2) . The fact that most of those infected with HSV are asymptomatic and yet may still be subclinically shedding virus further complicates efforts to slow the spread of transmission (3) . Therefore proper management of herpetic infections requires that the clinician be able to effectively diagnose those with HSV infection, to educate them regarding means of spread and symptoms indicative of infection, and to adequately treat infections which are identified in order to alleviate patient symptoms and slow the transmission of the virus. We review options for preventing infection, treating primary infections, and treating recurrent infections in order to accomplish these goals.     

HSV type specific serology in sexual health clinics: use, benefits, and who gets tested

OBJECTIVES: To determine which sexual health clinic clients were tested for herpes simplex virus (HSV) type specific antibodies and whether this test was useful for patient management. METHODS: Demographic, sexual and reproductive history, reasons for performing type specific serology, results, and benefits were derived from patient records from Parramatta Sexual Health Clinic for all patients who were tested between 13 September1993 and 31 December 2001. The value of serology was defined under five categories-diagnostic, counselling, initiating suppressive antiviral therapy, pregnancy counselling, and not useful. To establish whether patients tested for HSV were representative of clinic attendees, a sex matched "control" group was randomly selected. RESULTS: 382/886 (43.1%) were HSV-2 antibody positive and 774/884 (80.8%) were HSV-1 positive. The commonest reasons for requesting serology were having a partner with genital herpes (30%), undiagnosed recurrent genital ulceration (26%), and first episode of genital ulceration (22%). The test was of value in confirming the diagnosis in 57% of men and 60% of women with recurrent genital ulceration and in 28% of men and 40% of women with first episode genital herpes. In patients with a partner with genital herpes the test was of value in making a diagnosis in 27% men and 50% of women and in counselling 50% of women and 73% of men. Patients offered serology were older and more likely to have had genital herpes in the past than controls. CONCLUSION: Type specific serology should be recommended for the management of couples where one has genital herpes and the other apparently does not and in individuals with genital complaints suggestive of herpes.     

Frequency of acquisition of first-episode genital infection with herpes simplex virus from symptomatic and asymptomatic source contacts

Sixty-six source contacts of index patients with first-episode genital infection caused by herpes simplex virus (HSV) were evaluated for evidence of current or past HSV infections. Forty-three source contacts (65%) reported a history consistent with previous recurrent HSV infection or were experiencing a first episode of genital herpes when initially examined. However, 60% of these 43 contacts were not aware that they had transmissible HSV infection. Twenty-nine (67%) of the 43 individuals had had recent sexual contact with an index patient when lesions were present. All of the remaining 23 source contacts, who were without a history of symptoms consistent with HSV infection, had detectable neutralizing antibody to HSV; HSV type 2 was isolated from the cervix of two of these asymptomatic source contacts. Efforts to identify individuals with undiagnosed genital herpes and to instruct these individuals concerning the risk of disease transmission in the presence of lesions are needed if the rate of transmission is to be decreased; however, methods designed to decrease the rate of transmission by asymptomatic individuals must also be evaluated.     

Herpes simplex virus type 1 is the prevailing cause of genital herpes in the Tel Aviv area, Israel

BACKGROUND AND GOAL: The changing epidemiology of genital herpes with the increasing importance of herpes simplex virus (HSV) type 1 prompted a study on the relative prevalence of HSV-1 and HSV-2 among cases of genital herpes in the Tel Aviv area, Israel. STUDY DESIGN: A retrospective laboratory-based study of positive genital and nongenital herpes cultures performed at the Beilinson Medical Center between 1993 and 2002. Data regarding the number of isolates of each type and the age and sex of patients with genital lesions were retrieved from the database. Cultures were performed using Vero cells, and positive results were confirmed and typed by immunofluorescence. RESULTS: A total of 285 positive genital cultures and 659 positive nongenital cultures were recorded. HSV-1 was identified in 189 (66.3%) of the positive genital specimens and in 656 (99.55%) of the nongenital specimens. HSV-1 was isolated in 174 of 262 (66.4%) female subjects and 15 of 23 (65.2%) male subjects. The proportion of HSV-1 genital isolates was 72.7% in patients 15 to 24 years of age, 62% in those 25 to 44 years, and 46% in those aged 45 years or older. Overall, the annual isolation rate of genital HSV-1 has not changed markedly over the years. CONCLUSION: Herpes simplex virus type 1 has clearly been the predominant HSV type isolated from genital specimens in the Tel Aviv area over the last decade.     

Chancroid in Sheffield. A report of 22 cases diagnosed by isolating Haemophilus ducreyi in a modified medium.

The causative organism of chancroid, Haemophilus ducreyi, is generally considered to be very fastidious and its isolation, maintenance, and detailed study very demanding. In this study a modified medium was developed, which allowed the organism to be isolated more frequently than previously would have been expected. Twenty-two cases of chancroid were confirmed by the isolation of H ducreyi in 160 patients with genital ulceration examined over a one-year period. The cases were apparently unrelated, and in only five was there a history of recent sexual contact abroad. Concurrent infection with other sexually transmitted diseases was present in 18 (81.8%) patients, and in 14 (63.6%) both H ducreyi and herpes simplex virus were isolated form the same genital ulcers. Thus, these findings indicate that chancroid is underdiagnosed in England and that H ducreyi may frequently occur as a secondary invader of damaged genital skin and mucosa.     

Aquatic antagonists: lionfish stings

A clinical variant of genital herpes simplex virus (HSV) infection, recurrent lumbosacral HSV, occurs in bedridden hospitalized patients. We want to call attention to an uncommon pattern of HSV infection in the hospitalized bedridden patient seen by the dermatology consultation service in a large university hospital. HSV is characterized by a mixture of recurrent groups of herpetic vesicles in all stages of development, with multiple, persistent hyperpigmented patches bilaterally distributed over the lumbosacral (buttocks) area.     

Is HSV serology useful for the management of first episode genital herpes?

BACKGROUND: First episode genital herpes simplex virus (HSV) infections can be classified into three groups, primary genital herpes (no previous exposure to HSV), non-primary first episode (IgG antibody to HSV of the non-presenting type), and first episode with pre-existing IgG HSV antibodies. The use of IgM to classify first episode genital herpes has not been evaluated. OBJECTIVE: To evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of HSV-1 and HSV-2 IgM antibodies for the diagnosis of first episode genital herpes, when compared with clinical diagnosis. METHODS: Patients with a first clinical episode of genital herpes were recruited. Sera were tested for IgG antibodies to HSV-2 using an indirect enzyme linked immunosorbent assay (ELISA). Equivocal results were resolved by western blot. HSV-1 IgG and IgM and HSV-2 IgM antibodies were detected using western blot. RESULTS: 157 patients were recruited. 31 were excluded (missing data or no detectable antibodies and negative viral isolation). Therefore, 126 patients were included in the analysis. 23 (18.3%) had primary genital herpes, 34 (27.0%) non-primary first episode, and 69 (54.8%) had pre-existing genital herpes. The specificity and PPV of HSV IgM was 100%; the sensitivity was 79% and the NPV 85%. CONCLUSION: IgM HSV serology may be useful in the management of some patients with first episode genital herpes and provide an indication of the source of infection. Drawbacks include the low sensitivity and NPV, lack of availability, IgM antibodies may occasionally be produced in response to recurrent infection and, finally, IgM antibodies may take up to 10 days to develop and last 7-10 days.     

Control of STDs--the role of prophylactic vaccines against herpes simplex virus

OBJECTIVES: To summarise the current status of genital herpes simplex virus (HSV) vaccine development and provide a discussion of the potential benefits and limitations of genital herpes vaccines. METHODS: Literature review. RESULTS: Genital herpes simplex virus infection has a complex pathogenesis that has contributed to it becoming a serious worldwide problem. In an attempt to control the problem five different types of genital herpes vaccines have been developed. These include inactivated virion derived vaccines, adjuvanted subunit vaccines, vectored vaccines, replication limited live viral vaccines, genetically attenuated live viral vaccines, and nucleic acid vaccines. While available commercially in some parts of the world, inactivated virion derived vaccines have not been proved effective. Of the others, adjuvanted subunit vaccines, replication limited live viral vaccines, and nucleic acid vaccines are currently in clinical trials and vectored vaccines and genetically attenuated live viral vaccines are in preclinical development. CONCLUSION: With regard to HSV vaccines in general, it is reasonable to expect that the newer vaccines may protect the individual from developing symptomatic genital herpes but may not protect against asymptomatic viral infection. With widespread use HSV vaccines might help to prevent the spread of genital herpes.